Research in the treatment and causes of schizophrenia

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Vishwajit L Nimgaonkar, MD, PhD
Professor of Psychiatry and Human Genetics, University of Pittsburgh

Medicine, Culture, and Spirituality Conference
September 9, 2011

Published in: Health & Medicine
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Research in the treatment and causes of schizophrenia

  1. 1. Research in the treatment and causes of schizophrenia Vishwajit L Nimgaonkar, MD, PhD Professor of Psychiatry and Human Genetics, University of Pittsburgh [email_address]
  2. 2. Disclosure statement <ul><li>Vishwajit L. Nimgaonkar </li></ul><ul><li>has no conflict of interest in this presentation </li></ul>
  3. 3. Outline (vignettes) <ul><li>Diagnosis </li></ul><ul><li>Treatment </li></ul><ul><li>Causation </li></ul><ul><li>Research at Pittsburgh </li></ul><ul><li>Request for your help </li></ul>
  4. 4. Outline <ul><li>Diagnosis </li></ul><ul><li>Treatment </li></ul><ul><li>Causation </li></ul><ul><li>Research at Pittsburgh </li></ul><ul><li>Request for your help </li></ul>
  5. 5. Empirical Diagnosis (DSM IV) <ul><li>Two or more psychotic features: > 1 month </li></ul><ul><li>Impaired social / occupational function </li></ul><ul><li>Duration (6 months) </li></ul><ul><li>Exclude: </li></ul><ul><ul><li>Mood disorder, possible causative medical condition, substance abuse. </li></ul></ul>
  6. 6. Coming soon … <ul><li>DSM V criteria (due 2012) </li></ul><ul><ul><li>Lifespan diagnostic approach. </li></ul></ul><ul><ul><li>Emphasis on dimensional concepts. </li></ul></ul><ul><ul><li>Diagnostic specificity. </li></ul></ul><ul><ul><li>Interface between psychiatric and general medicine. </li></ul></ul><ul><ul><li>Gender and cross-cultural issues. </li></ul></ul><ul><ul><li>Remove schizoaffective disorder? </li></ul></ul>
  7. 7. Outline: <ul><li>Diagnosis </li></ul><ul><li>Treatment </li></ul><ul><li>Causation </li></ul><ul><li>Research at Pittsburgh </li></ul><ul><li>Request for your help </li></ul>
  8. 8. Patient Outcomes Research Team (PORT, Lehman et al, 1995 ….) <ul><li>Medications: Buchanan et al, 2010. </li></ul><ul><ul><li>http://www.ncbi.nlm.nih.gov/pubmed/19955390?dopt=Citation </li></ul></ul><ul><li>Psychosocial Rx: Dixon et al, 2010. </li></ul><ul><ul><li>http://schizophreniabulletin.oxfordjournals.org/content/36/1/48.full.pdf+html </li></ul></ul><ul><li>Levels of adherence? </li></ul>
  9. 9. Antipsychotic drugs <ul><li>Most significant benefit: </li></ul><ul><ul><li>PREVENTION OF RELAPSE </li></ul></ul><ul><li>Symptomatic improvement </li></ul><ul><li>Modest improvement: </li></ul><ul><ul><li>‘ negative’ symptoms </li></ul></ul><ul><ul><li>cognitive features </li></ul></ul><ul><ul><li>social function </li></ul></ul><ul><li>Efficacy / side effect profiles vary between patients. </li></ul>
  10. 10. Classical: first generation antipsychotic drugs <ul><li>Chlorpromazine (Largactil) </li></ul><ul><li>Haloperidol (Haldol) </li></ul><ul><li>Fluphenazine (Prolixin) </li></ul><ul><li>Ziprasidone (Geodon) </li></ul><ul><li>Clozapine (Clozaril): treatment resistant schizophrenia </li></ul>
  11. 11. Second generation antipsychotic drugs <ul><li>Risperidone (Risperdal) </li></ul><ul><li>Olanzapine (Zyprexa) </li></ul><ul><li>Quetiapine (Seroquel) </li></ul>
  12. 12. Most recent antipsychotic drugs <ul><li>Aripiprazole (Abilify) </li></ul><ul><li>Paliperidone (Invega)* </li></ul><ul><li>Asenapine (Saphris) </li></ul><ul><li>Iloperidone (Fanapt) </li></ul><ul><li>Lurasidone (Latuda) </li></ul><ul><li>* Risperidone metabolite </li></ul>
  13. 13. ‘ Newest’ antipsychotic drugs* * Cindy Holway, PharmD, MBA Drug Advantages Side effects/concerns Asenapine (Saphris) Sublingual, rapid absorption. Akathisia, oral hypoesthesia, somnolence. ? Hemodynamics. Iloperidone (Fanapt) Low EPS, low akathisia, little weight gain. Dizziness, orthostasis. ? QT prolongation. Lurasidone (Latuda) Pregnancy category B, low weight gain, low extra pyramidal symptoms. Akathisia, nausea. ? Use in moderate / severe renal impairment.
  14. 14. Adjunctive treatments (PORT, Dixon et al, 2010) <ul><li>Assertive Community Treatment </li></ul><ul><li>Supported Employment </li></ul><ul><li>Skills training </li></ul><ul><li>Cognitive Behavioral Therapy (+/-) </li></ul><ul><li>Token Economy Interventions (old data) </li></ul><ul><li>Family-Based Services </li></ul><ul><li>Alcohol and Substance Use Disorders </li></ul><ul><li>Weight Management </li></ul>
  15. 15. More evidence needed (PORT, Dixon et al, 2010) <ul><li>Cognitive remediation </li></ul><ul><li>Peer Support and Peer-Delivered Services </li></ul><ul><li>Interventions to Increase Adherence to Antipsychotic Medication </li></ul><ul><li>Psychosocial Treatments for Recent Onset Schizophrenia </li></ul>
  16. 16. Outline <ul><li>Diagnosis </li></ul><ul><li>Treatment </li></ul><ul><li>Causation </li></ul><ul><li>Research at Pittsburgh </li></ul><ul><li>Request for your help </li></ul>
  17. 17. Genetics: ‘tsunami’ <ul><li>Increased number of polymorphisms: </li></ul><ul><ul><li>genome-wide association studies (GWAS) ~1 million SNPs / person </li></ul></ul><ul><li>Coming soon: Whole genome sequencing. </li></ul>
  18. 18. GWAS: HLA variants and schizophrenia
  19. 19. HLA variants in schizophrenia: Pittsburgh studies
  20. 20. Copy number variations in schizophrenia <ul><ul><li>Odds ratios ~ 7 – 13 </li></ul></ul><ul><ul><li>Chromosome 22q11.2 </li></ul></ul><ul><ul><li>Chr. 1q21.1 </li></ul></ul><ul><ul><li>Chr.15q11.2 </li></ul></ul><ul><ul><li>Chr. 15q13.3 (autism / Angelman-Prader Willi S) </li></ul></ul>
  21. 21. Antibodies to Toxoplasma gondii in Patients with Schizophrenia: Meta-Analysis <ul><li>Torrey et al., Schizophr Bulletin (2007), 33 (3): 729-736. </li></ul><ul><li>Forty-two studies: 17 countries over 5 decades; 23 met selection criteria. </li></ul><ul><li>Combined odds ratio (OR): 2.73 </li></ul><ul><li>(95% C.I., 2.10 to 3.60; p < .000001). </li></ul>
  22. 22. Outline <ul><li>Diagnosis </li></ul><ul><li>Treatment </li></ul><ul><li>Causation </li></ul><ul><li>Research at Pittsburgh </li></ul><ul><li>Request for your help </li></ul>
  23. 23. Abnormalities in the auditory cortex <ul><li>Robert A. Sweet, M.D. </li></ul><ul><li>(Professor of Psychiatry and Neurology, Co-Associate Director for Research, MIRECC, VA Pittsburgh Healthcare System) </li></ul>
  24. 24. Small molecule modulation of dendritic spine structural plasticity to enhance persistence and prevent loss Prevention Auditory Cortex Clinical Feature Pathophysiology Pathology Vocal Emotion Discrimination Pitch Discrimination Pathogenesis Affective Impairment
  25. 25. <ul><li>K.N. Roy Chengappa, MD. </li></ul><ul><li>(Professor of Psychiatry, University of Pittsburgh) </li></ul><ul><li>L-Carnosine – A potent antioxidant has shown benefits for improving cognitive set-shifting and decreasing perseverative errors in a subgroup of people with schizophrenia. </li></ul><ul><ul><li>Unpublished. </li></ul></ul>Cognitive remediation: medications
  26. 26. Anti-herpes virus specific treatment and cognition in schizophrenia: a test-of-concept randomized double blind placebo controlled trial K M Prasad MD Assistant Professor of Psychiatry University of Pittsburgh ( unpublished)
  27. 27. Changes in neuropsychological scores with Valacyclovir ‘add on’
  28. 28. Yoga for cognitive remediation <ul><li>Bhatia et al, in press, Acta Psychiatrica Scandinavica </li></ul><ul><li>Federally funded trial in India </li></ul><ul><ul><li>conventional exercise as comparison </li></ul></ul><ul><ul><li>random allocation to treatment cells </li></ul></ul><ul><ul><li>‘ blind’ evaluation </li></ul></ul><ul><li>Pilot studies in the USA? </li></ul>
  29. 29. Outline <ul><li>Diagnosis </li></ul><ul><li>Treatment </li></ul><ul><li>Causation </li></ul><ul><li>Research at Pittsburgh </li></ul><ul><li>Request for your help </li></ul>
  30. 30. <ul><li>Comprehensive study of causation and pathogenesis </li></ul><ul><ul><li>Includes patients, relatives, controls </li></ul></ul><ul><ul><li>Diagnostic studies </li></ul></ul><ul><ul><li>Computerized cognitive evaluation </li></ul></ul><ul><ul><li>MRI studies </li></ul></ul><ul><ul><li>Genetic and environmental studies </li></ul></ul><ul><ul><li>Federally funded (NIMH) </li></ul></ul>A Family Study of Schizophrenia and Related Conditions
  31. 31. Participation details <ul><ul><ul><li>Families with > 2 closely related members with schizophrenia / schizoaffective disorder </li></ul></ul></ul><ul><ul><ul><ul><li>Parent / child; siblings </li></ul></ul></ul></ul><ul><ul><ul><ul><li>All relatives eligible </li></ul></ul></ul></ul><ul><ul><ul><li>Caucasian ethnicity </li></ul></ul></ul><ul><ul><ul><li>Voluntary and confidential . </li></ul></ul></ul><ul><ul><ul><li>No change in treatment. </li></ul></ul></ul><ul><ul><ul><li>One time. </li></ul></ul></ul><ul><ul><ul><li>Participant receive $ 175 + travel costs. </li></ul></ul></ul>
  32. 32. A Family Study of Schizophrenia and Related Conditions Please visit our table at the conference TOLL FREE: 1-877-363-5895 Fax: (412) 246 6350 WEB SITE: www.pitt.edu/~nimga

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